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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

Science China(Life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian newton ootecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

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Comparative population genomics reveals genetic basis underlying body size of domestic chickens

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Journal of Molecular Cell Biology 2016年第6期8卷 542-552页

作者： Ming-Shan Wang Yong-Xia Huo Yan Li newton ootecko Ling-Yan Su Hai-Bo Xu Shi-Fang Wu Min-Sheng Peng He-Qun Liu Lin Zeng David M.Irwin Yong-Gang Yao Dong-Dong Wu Ya-Ping Zhang State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204China College of Life Science Anhui UniversityHefei 230601China Laboratory for Conservation and Utilization of Bio-Resource Yunnan UniversityKunming 650091China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province Kunming Institute of ZoologyKunming 650223China Department of Laboratory Medicine and Pathobiology University of TorontoTorontoOntario M5S 1A8Canada Banting and Best Diabetes Centre University of TorontoTorontoOntario M5G 2C4Canada

Body size is the most important economic trait for animal production and *** hundreds of loci have been reported to be associated with growth trait and body weight in *** loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous ***,we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken(a famous ornamental chicken)based on 89 whole *** most significant signal was mapped to the BMP10 gene,whose expression was upregulated in the Yuanbao *** of BMP10 induced a significant decrease in body length by inhibiting angiogenic vessel development in *** addition,three other loci on chromosomes 1,2,and 24 were also identified to be potentially involved in the development of body *** results provide a paradigm shift in identification of novel loci controlling body size variation,availing a fast and efficient *** loci,particularly BMP10,add insights into ongoing research of the evolution of body size under artificial selection and have important implications for future chicken breeding.

关键词： body size artificial selection comparative population genomics domestication

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